DIFFERENTIAL AND TIME-DEPENDENT CHANGES IN GENE-EXPRESSION FOR TYPE-II CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE, 67 KDA GLUTAMIC-ACID DECARBOXYLASE, AND GLUTAMATE-RECEPTOR SUBUNITS IN TETANUS TOXIN-INDUCED FOCAL EPILEPSY/

To study potential molecular mechanisms of epileptogenesis in the neoc ortex, the motor cortex of rats was injected with tetanus toxin (TT), and gene expression for 67 kDa glutamic acid decarboxylase (GAD-67), t ype II calcium/calmodulin-dependent protein kinase (CaMKII), NMDA rece ptor subunit 1 (NR1), and AMPA receptor subunit 2 (GluR2) was investig ated by in situ hybridization histochemistry. Injections of 20-35 ng T T induced recurrent seizures after a postoperative period ranging from 4 to 13 d. A majority of rats perfused 5-7 d after TT injection showe d altered gene expression, but the changes varied in their areal exten t, ranging from most neocortical areas on the injected side in some ra ts to mainly the frontoparietal cortex or the motor cortex in others. Epileptic rats perfused 14 d after TT injection showed a focus of incr eased GAD-67 and NR1, and of decreased alpha-CaMKII and GluR2 mRNA lev els at the injection site. A zone of cortex surrounding the focus show ed changes in alpha-CaMKII, GAD-67, and NR1 mRNA levels that were reci procal to those in the focus. The results suggest that rr-induced seiz ure activity initially spread to a variable extent but was gradually r estricted 2-3 d after seizure onset. The focus and the surround showin g reciprocal changes in gene expression are thought to correspond to t he electrophysiologically identified epileptic focus and inhibitory su rround, respectively. The findings suggest that lateral inhibition bet ween neighboring cortical regions will be affected and contribute to a neurochemical segregation of an epileptic focus from surrounding cort ex.